Phylogenetic studies of cyanobacterial lichens

Phylogenetic studies of cyanobacterial lichens Lichens are symbiotic assemblages between fungi (mycobiont) and green algae (phycobiont) or/and cyanobacteria (cyanobiont). Fossil records show that lichen-like symbioses occurred already 600 million years ago. Lichen symbiosis has since then become an important life strategy for the Fungi, particularly for species in the phylum Ascomycota as approximately 98% of the lichenized fungal species are ascomycetes. The taxonomy of lichen associations is based on the mycobiont. We reconstructed, using DNA sequence data, hypotheses of phylogenetic relationships of lichen-forming fungi that include species associated with cyanobacteria. These hypotheses of phylogeny should form the basis for the taxonomy. They also allowed studies of the origin and the evolution of specific symbioses. Genetic diversity and phylogenetic relationships of symbiotic cyanobionts were also studied in order to examine selectivity of cyanobionts and mycobionts as well as possible co-evolution between partners involved in lichen associations. The suggested circumscription of the family Stereocaulaceae to include Stereocaulon and Lepraria is supported. The recently described crustose Stereocaulon species seem to be correctly placed in the genus, although Stereocaulon traditionally included only fruticose species. The monospecific crustose genus Muhria is also shown to be best placed in Stereocaulon. Family Lobariaceae as currently delimited is monophyletic. Within Lobariaceae genus Sticta including Dendriscocaulon dendroides form a monophyletic group while the genera Lobaria and Pseudocyphellaria are non-monophyletic. A new classification of Lobariaceae is obviously needed. Further studies are however required before a final proposal for a new classification can be made. Our results show that the cyanobacterial symbiotic state has been gained repeatedly in the Ascomycota while losses of symbiotic cyanobacteria appear to be rare. The symbiosis with green algae is confirmed to have been gained repeatedly in Ascomycota but also repeatedly lost. Cyanobacterial symbioses therefore seem to be more stable than green algal associations. Cyanobacteria are perhaps more beneficial for the lichen fungi and therefore maintained. The results indicate a dynamic association of the lichen symbiosis. This evolutionary instability will perhaps be important for the lichen fungi as the utilization of options will perhaps enable lichens to colonize new substrates and survive environmental changes. Some cyanobacterial lichen genera seem to be highly selective towards the cyanobiont while others form symbioses with a broad spectrum of cyanobacteria. No evidence of co-evolution between fungi and cyanobacteria in cyanolichens could be demonstrated.

The Frontiers of India's Biological Diversity

India has a long and rich history of tropical science. But here, as elsewhere in the tropical world, there are surprises to be discovered. One thinks immediately of the description, in December 2004, of a new species of macaque from India - the Arunachal macaque Macaca munzala. I use the word description deliberately, because this species was long known to the local people, and the species name rightly reflects this knowledge. Mun zala means "deep-forest monkey" in the language of the Dirang Monpa people of Tawang and West Kameng Districts of Arunachal Pradesh, where this species lives. The new macaque was discovered by science during field trips to these areas by Indian scientists from the Nature Conservation Foundation in Mysore, the National Institute of Advanced Studies in Bangalore, the Wildlife Conservation Society in New York, and the International Snow Leopard Trust. In this habitat, the largely Buddhist local community abstains from killing wildlife for food or sport, although the monkey has been reportedly shot for crop raiding. This species, one of the world's highest-living primate species, lives at altitudes between 1,600 and 3,500m, and is thus a veritable yeti.

Synthesis, structural and ferromagnetic properties of La1-xKxMnO3 (0.0 <= x <= 0.25) phases by solution combustion method

We describe the solution combustion synthesis and characterization of La1-xKxMnO3 (0.0 <= x <= 0.25) perovskite phases, which is a low temperature initiated, rapid route to prepare metal oxides. As-synthesized compounds are amorphous in nature; crystallinity was observed on heating at 800 degrees C for 5 min. Structural parameters were determined by the Rietveld refinement method using powder XRD data. Parent LaMnO3 compound crystallizes in the orthorhombic structure (space group Pbnm, No. 62). Potassium substituted compounds were crystallized with rhombohedral symmetry (space group R-3c, No. 167). The ratio of the Mn3+/Mn4+ was determined by the iodometric titration. The Fourier transform infrared spectrum (FTIR) shows two absorption bands for Mn-O stretching vibration (v, mode), Mn-O-Mn deformation vibration (v(b) mode) around 600 cm(-1) and 400 cm(-1) for the compositions, x = 0.0, 0.05 and 0-10. Four-probe electrical resistivity measurements reveal a composition controlled metal to insulator transition (TM-1), the maximum TM-1 was observed for the composition La0.85K0.15MnO3 at 287 K. Room temperature vibrating sample magnetometer data indicate that for the composition up to x = 0-10, the compounds are paramagnetic whereas composition with x = 0.15, 0.20 and 0.25 show magnetic moments of 27, 29 and 30 emu/g, respectively.

Synthesis of ZnO Nanoneedles on Flexible Polymer Substrates at Room Temperature by Activated Reactive Evaporation

ZnO nanoneedles were successfully deposited on flexible polymer substrates at room temperature by activated reactive evaporation. Neither a catalyst nor a template was employed in this synthesis. These synthesized needles measured 500 - 600 nm in length and its diameter varied from 30 - 15 nm from the base to the tip. The single-crystalline nature of the nanoneedle was observed by high-resolution transmission electron microscopy studies. The Raman studies on these nanoneedles had shown that they are oxygen deficient in nature. A possible growth mechanism has been proposed here, in which the nanoneedles nucleate and grow in the gas phase by vapor-solid mechanism.

The TRAM flap for breast reconstruction : Studies on perioperative cutaneous blood flow, vasoconstriction, and indices of obesity

Breast reconstruction is performed for 10-15 % of women operated on for breast cancer. A popular method is the TRAM (transverse rectus abdominis musculocutaneous) flap formed of the patient’s own abdominal tissue, a part of one of the rectus abdominis muscles and a transverse skin-subcutis area over it. The flap can be raised as a pedicled or a free flap. The pedicled TRAM flap, based on its nondominant pedicle superior epigastric artery (SEA), is rotated to the chest so that blood flow through SEA continues. The free TRAM flap, based on its dominant pedicle deep inferior epigastric artery (DIEA), is detached from the abdomen, transferred to the chest, and DIEA and vein are anastomosed to vessels on the chest. Cutaneous necrosis is seen in 5–60 % of pedicled TRAM flaps and in 0–15 % of free TRAM flaps. This study was the first one to show with blood flow measurements that the cutaneous blood flow is more generous in free than in pedicled TRAM flaps. After this study the free TRAM flap has exceeded the pedicled flap in popularity as a breast reconstruction method, although the free flap it is technically a more demanding procedure than the pedicled TRAM flap. In pedicled flaps, a decrease in cutaneous blood flow was observed when DIEA was ligated. It seems that SEA cannot provide sufficient blood flow on the first postoperative days. The postoperative cutaneous blood flow in free TRAM flaps was more stable than in pedicled flaps. Development of cutaneous necrosis of pedicled TRAM flaps could be predicted based on intraoperative laser Doppler flowmetry (LDF) measurements. The LDF value on the contralateral skin of the flap decreased to 43 ± 7 % of the initial value after ligation of the DIEA in flaps developing cutaneous necrosis during the next week. Endothelin-1 (ET-1) is a powerful vasoconstrictory peptide secreted by vascular endothelial cells. A correlation was found between plasma ET-1 concentrations and peripheral vasoconstriction developing during and after breast reconstructions with a pedicled TRAM flap. ET-1 was not associated with the development of cutaneous necrosis. Felodipine, a vasodilating calcium channel antagonist, had no effect on plasma ET-1 concentrations, peripheral vasoconstriction or development of cutaneous necrosis in free TRAM flaps. Body mass index and thickness of abdominal were not associated with cutaneous necrosis in pedicled TRAM flaps.

Surveillance in hereditary nonpolyposis colorectal cancer syndrome

Hereditary nonpolyposis colorectal cancer (HNPCC) is an inherited cancer predisposition syn-drome characterized by early onset colorectal cancer (CRC) and several other extra-colonic cancers, most commonly endometrial cancer (EC) and gastric cancer. Our aim was to evaluate the efficiency and results of the ongoing CRC and EC surveillance programs and to investigate the grounds for future gastric cancer screening by comparing the gastric biopsies of mutation positive and negative siblings in search for premalignant lesions. We also compared a new surveillance method, computerized tomographic colonoscopy (CTC) with optic colonoscopy. The patient material consisted of 579 family members from 111 Finnish HNPCC families al-most all harboring a known mismatch repair gene mutation. The efficacy of CRC and EC surveillance programs on HNPCC patients was evaluated by comparing the stage and survival of cancer cases detected with surveillance versus without. The performance of a new technique, CTC, was explored using a same-day colonoscopy as a reference standard. The use of intrauterine aspiration biopsies for EC surveillance was intro-duced for the first time in a HNPCC setting. Upper GI endoscopies were performed and biop-sies taken from mutation carriers and their mutation-negative siblings. The present surveillance program for CRC proved to be efficient. The CRC cases detected by surveillance were at a significantly more favorable stage than those in the non-surveilled group. This advantage was reflected in a significantly higher CRC-specific survival in the sur-veilled group. The performance of a new technique, CTC was found insufficient for polyp detection in this population in which every polyp, no matter the size, should be detected and removed. Colono-scopy was confirmed as a better surveillance modality than CTC. We could not observe any of the assumed differences in the gastric mucosa from mutation carriers and their mutation-negative siblings and no cases of gastric cancer were detected. The results gave no support for gastric surveillance. The EC surveillance program (transvaginal ultrasound and intra-uterine biopsy every 2-3 years) seemed to be efficient. It yielded several asymptomatic cancer cases and premalignant lesions. The stage distribution of the endometrial cancers in the group under surveillance tended to be more favorable than that of the mutation-positive, symptomatic EC patients who had no surveillance. None of the surveilled EC patients died of EC compared to six in the non-surveilled patients during the follow up. The improvement was, however, not statistically sig-nificant, thus far. Another observation was the good performance of endometrial aspiration biopsies used in this setting for the first time.

Triassic eclogite from northern Vietnam: inferences and geological significance

The first finding of low-temperature eclogites from the Indochina region is reported. The eclogites occur along the Song Ma Suture zone in northern Vietnam, which is widely regarded as the boundary between the South China and Indochina cratons. The major lithology of the area is pelitic schist that contains garnet and phengite with or without biotite, chloritoid, staurolite and kyanite, and which encloses blocks and lenses of eclogite and amphibolite. The eclogites commonly consist of garnet, omphacite, phengite, rutile, quartz and/or epidote with secondary barroisite. Omphacite is commonly surrounded by a symplectite of Na-poor omphacite and Na-rich plagioclase. In highly retrograded domains, diopside + tremolite + plagioclase symplectites replace the primary phases. Estimated peak-pressure metamorphic conditions based on isochemical phase diagrams for the eclogites are 2.1-2.2 GPa and 600-620 degrees C, even though thermobarometric results yield higher pressure and temperature conditions (2.6-2.8 GPa and 620-680 degrees C). The eclogites underwent a clockwise P-T trajectory with a post-peak-pressure increase of temperature to a maximum of > 750 degrees C at 1.7 GPa and a subsequent cooling during decompression to 650 degrees C and 1.3 GPa, which was followed by additional cooling before close-to-isothermal decompression to similar to 530 degrees C at 0.5 GPa. The surrounding pelitic schist (garnet-chloritoid-phengite) records similar metamorphic conditions (580-600 degrees C at 1.9-2.3 GPa) and a monazite chemical age of 243 +/- 4 Ma. A few monazite inclusions within garnet and the cores of some zoned monazite in garnet-phengite schist record an older thermal event (424 +/- 15 Ma). The present results indicate that the Indochina craton was deeply (> 70 km) subducted beneath the South China craton in the Triassic. The Silurian cores of monazite grains may relate to an older non-collisional event in the Indochina craton.

Temperature dependent structural properties of nanocrystalline SnS structures

This letter explores the structural behavior of nanocrystalline tin mono sulfide (SnS) structures with respect to temperature (100-600 K). These studies emphasize that the structural properties of SnS nanocrystalline structures depend on the surrounding temperature. The lattice parameters of SnS nanocrystals slightly varied like their microstructures with the increase of temperature. These changes strongly influence the optical properties of SnS nanostructures. On the other hand, the structures exhibited higher strain (similar to 0.44%) than that of microstructured (0.3%) and bulk (0.12%) counterparts. The observed results are discussed under the light of existing concepts and reported.

Depression, Anxiety, Psychiatric Comorbidity and Dimensions of Temperament and Personality

This study is part of the Mood Disorders Project conducted by the Department of Mental Health and Alcohol Research, National Public Health Institute, and consists of a general population survey sample and a major depressive disorder (MDD) patient cohort from Vantaa Depression Study (VDS). The general population survey study was conducted in 2003 in the cities of Espoo and Vantaa. The VDS is a collaborative depression research project between the Department of Mental Health and Alcohol Research of the National Public Health Institute and the Department of Psychiatry of the Peijas Medical Care District (PMCD) beginning in 1997. It is a prospective, naturalistic cohort study of 269 secondary-level care psychiatric out- and inpatients with a new episode of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) MDD. In the general population survey study, a total of 900 participants (300 from Espoo, 600 from Vantaa) aged 20 70 years were randomly drawn from the Population Register Centre in Finland. A self-report booklet, including the Eysenck Personality Inventory (EPI), the Temperament and Character Inventory Revised (TCI-R), the Beck Depression Inventory and the Beck Anxiety Inventory was mailed to all subjects. Altogether 441 participants responded (94 returned only the shortened version without TCI-R) and gave their informed consent. VDS involved screening all patients aged 20-60 years (n=806) in the PMCD for a possible new episode of DSM-IV MDD. 542 consenting patients were interviewed with a semi-structured interview (the WHO Schedules for Clinical Assessment in Neuropsychiatry, version 2.0). 269 patients with a current DSM-IV MDD were included in the study and further interviewed with semi-structured interviews to assess all other axis I and II psychiatric diagnoses. Exclusion criteria were DSM-IV bipolar I and II, schizoaffective disorder, schizophrenia or another psychosis, organic and substance-induced mood disorders. In the present study are included those 193 (139 females, 54 males) individuals who could be followed up at both 6 and 18 months, and their depression had remained unipolar. Personality was investigated with the EPI. Personality dimensions associated not only to the symptoms of depression, but also to the symptoms of anxiety among general population and in depressive patients, as well as to comorbid disorders in MDD patients, supporting the dimensional view of depression and anxiety. Among the general population High Harm Avoidance and low Self-Directedness associated moderately, whereas low extraversion and high neuroticism strongly with the depressive and anxiety symptoms. The personality dimensions, especially high Harm Avoidance, low Self-Directedness and high neuroticism were also somewhat predictive of self-reported use of health care services for psychiatric reasons, and lifetime mental disorder. Moreover, high Harm Avoidance associated with a family history of mental disorder. In depressive patients, neuroticism scores were found to decline markedly and extraversion scores to increase somewhat with recovery. The predictive value of the changes in symptoms of depression and anxiety in explaining follow-up neuroticism was about 1/3 of that of baseline neuroticism. In contrast to neuroticism, the scores of extraversion showed no dependence on the symptoms of anxiety, and the change in the symptoms of depression explained only 1/20 of the follow-up extraversion compared with baseline extraversion. No evidence was found of the scar effect during a one-year follow-up period. Finally, even after controlling for symptoms of both depression and anxiety, depressive patients had a somewhat higher level of neuroticism (odds ratio 1.11, p=0.001) and a slightly lower level of extraversion (odds ratio 0.92, p=0.003) than subjects in the general population. Among MDD patients, a positive dose-exposure relationship appeared to exist between neuroticism and prevalence and number of comorbid axis I and II disorders. A negative relationship existed between level of extraversion and prevalence of comorbid social phobia and cluster C personality disorders. Personality dimensions are associated with the symptoms of depression and anxiety. Futhermore these findings support the hypothesis that high neuroticism and somewhat low extraversion might be vulnerability factors for MDD, and that high neuroticism and low extraversion predispose to comorbid axis I and II disorders among patients with MDD.

Thermal properties and thermal shock resistance of γ-Y 2Si2O7

Thermal properties, namely, Debye temperature, thermal expansion coefficient, heat capacity, and thermal conductivity of γ-Y 2Si2O7, a high-temperature polymorph of yttrium disilicate, were investigated. The anisotropic thermal expansions of γ-Y2Si2O7 powders were examined using high-temperature X-ray diffractometer from 300 to 1373 K and the volumetric thermal expansion coefficient is (6.68±0.35) × 10-6 K-1. The linear thermal expansion coefficient of polycrystalline γ-Y2Si2O7 determined by push-rod dilatometer is (3.90±0.4) × 10-6 K-1, being very close to that of silicon nitride and silicon carbide. Besides, γ-Y2Si2O7 displays a low-thermal conductivity, with a κ value measured below 3.0 W·(m·K) -1 at the temperatures above 600 K. The calculated minimum thermal conductivity, κmin, was 1.35 W·(m·K) -1. The unique combination of low thermal expansion coefficient and low-thermal conductivity of γ-Y2Si2O7 renders it a very competitive candidate material for high temperature structural components and environmental/thermal-barrier coatings. The thermal shock resistance of γ-Y2Si2O7 was estimated by quenching dense materials in water from various temperatures and the critical temperature difference, ΔTc, was determined to be 300 K.

Preterm delivery and selected biomarkers : phosphorylated insulin-like growth factor-binding protein-1 and matrix metalloproteinase-8 – in cervical fluid

Premature delivery is a major cause of neonatal morbidity and mortality. The incidence of premature deliveries has increased around the world. In Finland 5.3%, or about 3,000 children per year are born prematurely, before 37 weeks of gestation. The corresponding figure in the United States is about 13%. The morbidity and mortality are highest among infants delivered before 32 weeks of gestation - about 600 children each year in Finland. Approximately 70% of premature deliveries are unexplained. Preterm delivery can be caused by an asympto-matic infection between uterus and the fetal membranes, such can begin already in early pregnancy. It is difficult to predict preterm delivery, and many patients are therefore unnecessarily admitted to hospital for observation and exposed to medical treatments. On the other hand, the high risk women should be identified early for the best treatment of the mother and preterm infant. --- In the prospective study conducted at the Department of Obstetric and Gynecology, Helsinki University Central Hospital two biochemical inflammation related markers were measured in the lower genital tract fluids of asymp-tomatic women in early and mid pregnancy in an order to see whether these markers could identify women with an increased risk of preterm delivery. These biomarkers were phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) and matrix metalloproteinase-8 (MMP-8). The study involved 5180 asymptomatic pregnant women, examined during the first and second ultrasound screening visits. The study samples were taken from the vagina and cervicix. In addition, 246 symptomatic women were studied (pregnancy weeks 22 – 34). The study showed that increased phIGFBP-1 concentration in cervical canal fluid in early pregnancy increased the risk for preterm delivery. The risk for very premature birth (before 32 weeks of gestation) was nearly four-fold. Low MMP-8 concentration in mid pregnancy increased the risk of subsequent premature preterm rupture of fetal membranes (PPROM). Significantly high MMP-8 concentrations in the cervical fluid increased the risk for prema-ture delivery initiated by preterm labour with intact membranes. Among women with preterm contractions the shortened cervical length measured by ultrasound and elevated cervical fluid phIGFBP-1 both predicted premature delivery. In summary, because of the relatively low sensitivity of cervical fluid phIGFBP-1 this biomarker is not suitable for routine screening, but provides an additional tool in assessing the risk of preterm delivery. Cervical fluid MMP-8 is not useful in early or mid pregnancy in predicting premature delivery because of its dual role. Further studies on the role of MMP-8 are therefore needed. Our study confirms that phIGFBP-1 testing is useful in predicting pre-term delivery.

Testicular function in adolescent boys with Klinefelter syndrome

Klinefelter syndrome (KS) is the most frequent karyotype disorder of male reproductive function. Since its original clinical description in 1942 and the identification of its chromosomal basis 47,XXY in 1959, the typical KS phenotype has become well recognized, but the mechanisms behind the testicular degeneration process have remained unrevealed. This prospective study was undertaken to increase knowledge about testicular function in adolescent KS boys. It comprised a longitudinal follow-up of growth, pubertal development, and serum reproductive hormone levels in 14 prepubertal and pubertal KS boys. Each boy had a testicular biopsy that was analyzed with histomorphometric and immunohistochemical methods. The KS boys had sufficient testosterone levels to allow normal onset and progression of puberty. Their serum testosterone levels remained within the low-normal range throughout puberty, but from midpuberty onwards, findings like a leveling-off in testosterone and insulin-like factor 3 (INSL3) concentrations, high gonadotropin levels, and exaggerated responses to gonadotropin-releasing hormone stimulation suggest diminished testosterone secretion. We also showed that the Leydig cell differentiation marker INSL3 may serve as a novel marker for onset and normal progression of puberty in boys. In the KS boys the number of germ cells was already markedly lower at the onset of puberty. The pubertal activation of the pituitary-testicular axis accelerated germ cell depletion, and germ cell differentiation was at least partly blocked at the spermatogonium or early primary spermatocyte stages. The presence of germ cells correlated with serum reproductive hormone levels. The immature Sertoli cells were incapable of transforming to the adult type, and during puberty the degeneration of Sertoli cells increased markedly. The older KS boys displayed an evident Leydig cell hyperplasia, as well as fibrosis and hyalinization of the interstitium and peritubular connective tissue. Altered immunoexpression of the androgen receptor (AR) suggested that in KS boys during puberty a relative androgen deficiency develops at testicular level. The impact of genetic features of the supernumerary X chromosome on the KS phenotype was also studied. The present study suggests that parental origin of the supernumerary X chromosome and the length of the CAG repeat of the AR gene influence pubertal development and testicular degeneration. The current study characterized by several means the testicular degeneration process in the testes of adolescent KS boys and confirmed that this process accelerates at the onset of puberty. Although serum reproductive hormone levels indicated no hypogonadism during early puberty, the histological analyses showed an already markedly reduced fertility potential in prepubertal KS boys. Genetic features of the X chromosome affect the KS phenotype.

Migraine Comorbidities : A Clinical and Molecular Genetic Study

Migraine is a highly prevalent disease, and despite several important breakthroughs there are still a many questions unanswered in the clinical, genetic and pathophysiological aspects of migraine research. Migraine has been linked to several other diseases such as epilepsy and stroke, but there are still unsolved issues concerning the true nature of these associations. Three genes predisposing to hemiplegic migraine and several loci associated to migraine have been identified, but so far no genes responsible for common forms of migraine have been recognized. Triptans have provided an important step in migraine treatment, but their usefulness in rare forms of migraine have been controversial. The Finnish Migraine Gene Project (FMGP) includes more than 1600 families and 7500 individuals. We evaluated comorbidity from 1000 consecutive subjects in the FMGP. To search for novel loci, we performed a genome-wide linkage scan in 36 families with high prevalences of migraine with visual aura. We collected 76 subjects from the FMGP who suffer from hemiplegic migraine and have used triptans. Finally, to study possible links between stroke and migraine we evaluated the prevalence of migraine in subjects with cervical artery dissection (CAD) and healthy controls. Migraine was associated with increased prevalence of allergy, hypotension and psychiatric diseases. Additionally, men suffering from migraine with aura had increased prevalence of epilepsy and stroke. Further evidence of association between migraine and epilepsy was found in our linkage study. The parametric two-point linkage analysis showed significant evidence of linkage between migraine aura and a locus on 9q21-q22. Interestingly, the same locus has been associated with occipitotemporal epilepsy. CAD seems to be a migraine risk factor, and therefore a link between stroke and migraine. Notably, CAD seems to alleviate migraine activity further indicating the association between these two conditions. Despite the contraindications of triptans, it seems that they are safe and effective in the abortive treatment of hemiplegic migraine.

Pharmacogenetics of SLCO1B1: Population genetics and effect on statins

Kohonneiden kolesterolipitoisuuksien alentamisessa käytettävien statiinien hyödyt sydän- ja verisuonisairauksien estossa on vahvasti osoitettu ja niiden käyttö on niin Suomessa kuin muuallakin maailmassa kasvanut voimakkaasti – Suomessa statiininkäyttäjiä on noin 600 000. Statiinilääkitys on pitkäaikaisessakin käytössä melko hyvin siedetty, mutta yleisimpinä haittavaikutuksina voi ilmetä lihasheikkoutta, -kipua ja -kramppeja, jotka voivat edetä jopa henkeä uhkaavaksi lihasvaurioksi. Lihashaittariski suurenee suhteessa statiiniannokseen ja plasman statiinipitoisuuksiin. Statiinien plasmapitoisuuksissa, tehossa ja haittavaikutusten ilmenemisessä on suuria potilaskohtaisia eroja. SLCO1B1-geenin koodaama OATP1B1-kuljetusproteiini kuljettaa monia elimistön omia aineita ja lääkeaineita verenkierrosta solukalvon läpi maksasoluun, mm. statiineja, joiden kolesterolia alentava vaikutus ja poistuminen elimistöstä tapahtuvat pääosin maksassa. Erään SLCO1B1-geenin nukleotidimuutoksen (c.521T>C) tiedetään heikentävän OATP1B1:n kuljetustehoa. Tässä väitöskirjatyössä selvitettiin SLCO1B1-geenin perinnöllistä muuntelua suomalaisilla ja eri väestöissä maailmanlaajuisesti. Lisäksi selvitettiin SLCO1B1:n muunnosten vaikutusta eri statiinien pitoisuuksiin (farmakokinetiikka) ja vaikutuksiin (farmakodynamiikka) sekä kolesteroliaineenvaihduntaan. Näihin tutkimuksiin valittiin SLCO1B1-genotyypin perusteella terveitä vapaaehtoisia koehenkilöitä, joille annettiin eri päivinä kerta-annos kutakin tutkittavaa statiinia: fluvastatiinia, pravastatiinia, simvastatiinia, rosuvastatiinia ja atorvastatiinia. Verinäytteistä määritettiin plasman statiinien ja niiden aineenvaihduntatuotteiden sekä kolesterolin ja sen muodostumista ja imeytymistä kuvaavien merkkiaineiden pitoisuuksia. Toiminnallisesti merkittävien SLCO1B1-geenimuunnosten esiintyvyydessä todettiin suuria eroja eri väestöjen välillä. Suomalaisilla SLCO1B1 c.521TC-genotyypin (geenimuunnos toisessa vastinkromosomissa) esiintyvyys oli noin 32 % ja SLCO1B1 c.521CC-genotyypin (geenimuunnos molemmissa vastinkromosomeissa) esiintyvyys noin 4 %. Globaalisti geenimuunnosten esiintyvyys korreloi maapallon leveyspiirien kanssa siten, että matalaan transportteriaktiivisuuteen johtavat muunnokset olivat yleisimpiä pohjoisessa ja korkeaan aktiivisuuteen johtavat päiväntasaajan lähellä asuvilla väestöillä. SLCO1B1-genotyypillä oli merkittävä vaikutus statiinien plasmapitoisuksiin lukuun ottamatta fluvastatiinia. Simvastatiinihapon plasmapitoisuudet olivat keskimäärin 220 %, atorvastatiinin 140 %, pravastatiinin 90 % ja rosuvastatiinin 70 % suuremmat c.521CC-genotyypin omaavilla koehenkilöillä verrattuna normaalin c.521TT-genotyypin omaaviin. Genotyypillä ei ollut merkittävää vaikutusta minkään statiinin tehoon tässä kerta-annostutkimuksessa, mutta geenimuunnoksen kantajilla perustason kolesterolisynteesinopeus oli suurempi. Tulokset osoittavat, että SLCO1B1 c.521T>C geenimuunnos on varsin yleinen suomalaisilla ja muilla ei-afrikkalaisilla väestöillä. Tämä geenimuunnos voi altistaa erityisesti simvastatiinin, mutta myös atorvastatiinin, pravastatiinin ja rosuvastatiinin, aiheuttamille lihashaitoille suurentamalla niiden plasmapitoisuuksia. SLCO1B1:n geenimuunnoksen testaamista voidaan tulevaisuudessa käyttää apuna valittaessa sopivaa statiinilääkitystä ja -annosta potilaalle, ja näin parantaa sekä statiinihoidon turvallisuutta että tehoa.

Synthesis of Diketopyrrolopyrrole Containing Copolymers: A Study of Their Optical and Photovoltaic Properties

The diketopyrrolopyrrole-based copolymers PDPP-BBT and TDPP-BBT were synthesized and used as donor for bulk heterojunction photovoltaic devices. The photophysical properties of these polymers showed absorption in the range 500-600 nm with a maximum peak around 563 nm, while TDPP-BBT showed broadband absorption in the range 620 - 800 nm with a peak around 656 nm. The power conversion efficiencies (PCE) of the polymer solar cells based on these copolymers and [6,6]-phenyl C61 butyric acid methyl ester (PCBM) were 0.68% (as cast PDPP-BBT:PCBM), 1.51% (annealed PDPP-BBT:PCBM), 1.57% (as cast TDPPBBT: PCBM), and 2.78% (annealed TDPP-BBT:PCBM), under illumination of AM 1.5 (100 mW/cm2). The higher PCE for TDPP-BBT-based polymer solar cells has been attributed to the low band gap of this copolymer as compared to PDPP-BBT, which increases the numbers of photogenerated excitons and corresponding photocurrent of the device. These results indicate that PDPP-BBT and TDPP-BBT act as excellent electron donors for bulk heterojunction devices.